By using DNA hybridization, in situ hybridization, chromosome inversion mapping and interspecific hybridization, we studied Drosophila genome organization and evolution. The inversion breakpoints tended to cluster in heterchromatic sites (Yoon and Richardson, 1976), heterchromatin appeared de novo with the first break in the phylogeny, the sites often show ectopic pairing with highly repetitious DNA sequences at each site and in connecting strands (Triantaphillides and Richardson, Ms.), and the inversions achieved replacement of the primitive gene order with an average selection intensity of 1%. In other studies, only the D. arisonensis nucleolar organizer region (NOR) on the X-chromosome was active in the arizonensis-mulleri hybrid females, while a latent NOR in the "dot" chromosome was activated in the male hybrids with only an inactive mulleri NOR on the X-chromosome (Bicudo and Richardson, Ms.). Morphological modifications of the hybrid male included those that resembled the "bobbed" phenotype in D. melanogaster. In situ hybridization of satellites in D. nasutoides failed to reveal any localization at centromeres (Lee, Arrighi, Hsu and Wheeler, Ms., but all four satellites were localized in the metaphase arms, especially in the giant metacentric heterochromatic chromosome. DNA hybridization results with intermediate repetitious and single copy sequences agreed with polytene chromosome inversion phylogenies. At a change of about 1 base pair/yr., the divergence rate corresponded to the geological records where the species have evolved (Triantaphillides and Richardson, Ms.), while the same rate of divergence between the Hawaiian species and the closest known mainland relatives suggests either twice as rapid divergence, or earlier colonization of the archipellago, or an unknown closer mainland relative. (Richardson, Triantaphillides and Turner, Ms.).